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Updated: May 19, 2026

In vitro Assessment of Cardiac Reprogramming by Measuring Cardiac Specific Calcium Flux with a GCaMP3 Reporter
Published on: February 22, 2022
Rem-GTPase regulates cardiac myocyte L-type calcium current
Janos Magyar1, Carmen E Kiper, Gail Sievert
1Department of Physiology, University of Kentucky College of Medicine, Lexington, USA.
The RGK protein Rem regulates L-type calcium channels (LTCC) in heart cells. Rem knockout mice show altered calcium currents, impacting heart cell function in vivo.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Ion Channel Regulation
Background:
- L-type calcium channels (LTCC) are crucial for calcium homeostasis.
- RGK-class proteins are known to regulate LTCC in experimental systems.
- The in vivo physiological role of RGK-LTCC interactions in the heart remains unclear.
Purpose of the Study:
- To investigate the role of the RGK protein Rem in modulating native L-type calcium channel current (I(Ca,L)) in murine cardiomyocytes.
- To test the hypothesis that Rem influences cardiac I(Ca,L) in vivo.
Main Methods:
- Generation of Rem knockout mice (Rem(-/-)).
- Assessment of I(Ca,L) density, activation, kinetics, inactivation, and facilitation in isolated cardiomyocytes.
- Evaluation of Ca(2+) handling properties, including twitch transient amplitude.
- Computer simulations and immunoblot analysis to explore underlying mechanisms.
Main Results:
- Rem(-/-) ventricular cardiomyocytes exhibited increased I(Ca,L) density and a positive shift in activation voltage.
- Beta-adrenergic stimulation normalized the activation shift in Rem(-/-) cells.
- Despite increased I(Ca,L) density, Rem(-/-) cardiomyocytes showed reduced Ca(2+) twitch transient amplitude.
- Relative dephosphorylation of LTCC in Rem(-/-) cells was suggested as a cause for the paradoxical decrease in Ca(2+) transients.
Conclusions:
- This study provides the first in vivo evidence that an RGK protein (Rem) influences cardiac L-type calcium channel function in myocytes.
- Loss of Rem leads to altered cardiac calcium current properties and paradoxical effects on Ca(2+) transients.
- These findings highlight the physiological importance of RGK proteins in regulating cardiac ion channel function and calcium handling.
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